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A novel role for CFTR interaction with LH and FGF in azoospermia and epididymal maldevelopment caused by cryptorchidism. CFTR与LH和FGF相互作用在隐睾引起的无精子症和附睾发育不良中的新作用。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-06-21 DOI: 10.1186/s12610-022-00160-0
Faruk Hadziselimovic, Gilvydas Verkauskas, Michael Stadler

Cryptorchidism occurs frequently in children with cystic fibrosis. Among boys with cryptorchidism and abrogated mini-puberty, the development of the epididymis and the vas deferens is frequently impaired. This finding suggests that a common cause underlies the abnormal development of Ad spermatogonia and the epididymis. The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette transporter protein that acts as a chloride channel. The CFTR gene has been associated with spermatogenesis and male fertility. In boys with cryptorchidism, prepubertal hypogonadotropic hypogonadism induces suboptimal expression of the ankyrin-like protein gene, ASZ1, the P-element induced wimpy testis-like gene, PIWIL, and CFTR. The abrogated expression of these gene leads to transposon reactivation, and ultimately, infertility. Curative gonadotropin-releasing hormone agonist (GnRHa) treatment stimulates the expression of CFTR and PIWIL3, which play important roles in the development of Ad spermatogonia and fertility. Furthermore, GnRHa stimulates the expression of the epididymal androgen-sensitive genes, CRISP1, WFDC8, SPINK13, and PAX2, which thereby promotes epididymal development. This review focuses on molecular evidence that favors a role for CFTR in cryptorchidism-induced infertility. Based on information available in the literature, we interpreted our RNA-Seq expression data obtained from samples before and after randomized GnRHa treatment in boys with bilateral cryptorchidism. We propose that, in boys with cryptorchidism, CFTR expression is controlled by luteinizing hormone and testosterone. Moreover, CFTR regulates the activities of genes that are important for fertility and Wolffian duct differentiation.

隐睾症常见于囊性纤维化患儿。在隐睾和青春期缩短的男孩中,附睾和输精管的发育经常受损。这一发现表明,一个共同的原因,背后的异常发育的精原细胞和附睾。囊性纤维化跨膜传导调节因子(CFTR)是一种atp结合盒转运蛋白,作为氯离子通道。CFTR基因与精子发生和男性生育能力有关。在患有隐睾症的男孩中,青春期前促性腺功能低下会导致锚蛋白样蛋白基因ASZ1、p元素诱导的睾丸样基因PIWIL和CFTR的亚理想表达。这些基因的废弃表达导致转座子再激活,最终导致不育。治疗性促性腺激素释放激素激动剂(GnRHa)可刺激CFTR和PIWIL3的表达,这两种基因在Ad精原细胞的发育和生育中发挥重要作用。此外,GnRHa刺激附睾雄激素敏感基因CRISP1、WFDC8、SPINK13、PAX2的表达,从而促进附睾发育。本文综述了CFTR在隐睾致不孕症中的作用。基于文献资料,我们对双侧隐睾男孩随机GnRHa治疗前后样本的RNA-Seq表达数据进行了解释。我们认为,在男孩隐睾症中,CFTR的表达受黄体生成素和睾酮的控制。此外,CFTR还调节了对生育和沃尔夫管分化重要的基因的活性。
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引用次数: 1
Association between metabolic disorders and seminal plasma miRNA levels: a pilot study. 代谢紊乱与精浆miRNA水平的关联:一项初步研究。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-06-07 DOI: 10.1186/s12610-022-00159-7
Sarah Saget, Laurent Kappeler, Valérie Grandjean, Patricia Leneuve, Isabelle Berthaut, Céline Faure, Sébastien Czernichow, Chrystèle Racine, Rachel Lévy, Charlotte Dupont

Background: Excess weight and metabolic disorders have a negative impact on male reproductive functions. The mechanisms involved are numerous and complex and epigenetic mechanisms may also be involved, notably through the small non-coding RNAs. Among them, microRNAs (miRNAs) are of particular interest. This preliminary study aimed to identify the miRNAs differentially enriched in seminal plasma related to metabolic disorders and if some are also associated with spermatic parameters alterations. One hundred and sixty men between 18 to 45 years, partners of infertile couple, were included in this cohort. The miRNAs associated with metabolism were selected from the literature and assayed by quantitative real-time PCR using TaqMan gene expression assays. A subset of those with an interesting profile in seminal plasma were secondarily tested in blood.

Results: Among the 11 selected miRNAs, seven were detected in seminal plasma (miR10b, miR19a, miR19b, miR34b, miR34c, miR133b, miRlet7c). A negative correlation was observed between seminal miR19a levels and metabolic syndrome, blood glucose and C-peptide. Seminal miR19b levels were also negatively correlated with metabolic syndrome. Seminal miR34c levels were negatively correlated with body mass index (BMI) and waist circumference. Seminal miR133b levels were positively correlated with BMI, waist circumference and leptin levels. Interestingly, modifications of miRNAs in seminal plasma seem specific since highlighted above correlations were not retrieved in the blood plasma for the miR19a, 19b, 10b, 34c.

Conclusion: Few metabolic and anthropometric disorders are correlated with the level of specific miRNAs in seminal plasma. Further studies will be required to decipher if other small non-coding RNAs may also be correlated with metabolic and anthropometric disorders and to assess their potential implication in the alteration of reproductive functions in men with obesity or metabolic disorders.

Clinical study: Metabolic Syndrome and Male Infertility (Metasperme): Trial registration:  NCT01974947 . Registered 18 July 2013.

背景:超重和代谢紊乱对男性生殖功能有负面影响。所涉及的机制众多而复杂,表观遗传机制也可能参与其中,特别是通过小的非编码rna。其中,microRNAs (miRNAs)尤其令人感兴趣。这项初步研究旨在确定与代谢紊乱相关的精浆中差异富集的mirna,以及是否有些mirna也与精子参数改变有关。160名年龄在18到45岁之间的男性,不育夫妇的伴侣,包括在这个队列中。从文献中选择与代谢相关的mirna,采用TaqMan基因表达法进行实时荧光定量PCR检测。在精浆中具有有趣特征的子集在血液中进行了二次测试。结果:在所选的11个mirna中,在精浆中检测到7个mirna (miR10b、miR19a、miR19b、miR34b、miR34c、miR133b、miRlet7c)。精液miR19a水平与代谢综合征、血糖、c肽呈负相关。精液miR19b水平也与代谢综合征呈负相关。精液miR34c水平与体重指数(BMI)和腰围呈负相关。精液miR133b水平与BMI、腰围和瘦素水平呈正相关。有趣的是,精浆中mirna的修饰似乎是特异性的,因为上面强调的相关性并没有在血浆中检索到miR19a, 19b, 10b, 34c。结论:少数代谢和人体测量障碍与精浆中特异性mirna的水平相关。需要进一步的研究来破译其他小的非编码rna是否也可能与代谢和人体测量障碍相关,并评估它们对肥胖或代谢障碍男性生殖功能改变的潜在影响。临床研究:代谢综合征与男性不育(Metasperme):试验注册号:NCT01974947。注册于2013年7月18日。
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引用次数: 0
The NLRP3 inflammasome: molecular activation and regulation in spermatogenesis and male infertility; a systematic review NLRP3炎性小体在精子发生和男性不育中的分子激活与调控系统回顾
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-05-30 DOI: 10.1186/s12610-022-00157-9
M. Tavalaee, M. Rahmani, J. Drevet, M. Nasr-Esfahani
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引用次数: 12
Sarcoidosis of the spermatic cord – case report and literature review 精索结节病1例报告并文献复习
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-05-19 DOI: 10.1186/s12610-022-00158-8
M. Ostrowska, P. Świniarski, A. Ostrowski, F. Kowalski, J. Adamowicz, D. Grzanka, T. Drewa, K. Juszczak
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引用次数: 2
ICSI outcomes for infertile men with severe or complete asthenozoospermia 患有严重或完全弱精子症的不育男性的ICSI结果
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-04-05 DOI: 10.1186/s12610-022-00155-x
Tong Chen, Demin Fan, Xianlong Wang, Changlin Mao, Yaru Chu, Haobo Zhang, Wen Liu, S. Ding, Qingyong Liu, Mingzhen Yuan, Jiaju Lu
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引用次数: 4
Lipopolysaccharide-preconditioned allogeneic adipose-derived stem cells improve erectile function in a rat model of bilateral cavernous nerve injury. 脂多糖预处理异体脂肪干细胞改善双侧海绵状神经损伤大鼠模型的勃起功能。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-03-25 DOI: 10.1186/s12610-022-00156-w
Zhenbin Zhang, Pan Nie, Wende Yang, Xiaolei Ma, Zehong Chen, Hongbo Wei

Background: Erectile dysfunction (ED) often occurs due to cavernous nerve injury (CNI) after colorectal surgery. Cell-based therapies have great potential for the treatment of CNI-related ED; however, it needs to be optimised. In this study, we explored the therapeutic effects of lipopolysaccharide-preconditioned allogeneic adipose-derived stem cells (L-ADSCs) on CNI-induced ED in rats.

Results: The results of this in vitro study revealed that low-dose lipopolysaccharide could increase the viability of ADSCs, inhibit caspase 3 activation induced by hydrogen peroxide and promote cell migration. Compared with the ADSC supernatant, the L-ADSC supernatant could better reduce fibrosis in the corpus cavernosum smooth muscle cells induced by transforming growth factor-beta 1 protein. In the in vivo study, it was compared to ADSCs therapy, where the L-ADSCs therapy indicated that could better improve erectile function by increasing smooth muscle content and alleviating penile fibrosis in rats 2 weeks after CNI. The outcome may be related to the increase in the hepatocyte growth factor content in the corpus cavernosum and myelin basic protein in the major pelvic ganglion.

Conclusions: L-ADSC treatment may be a promising approach for restoring erectile function after CNI.

背景:结直肠手术后海绵状神经损伤常导致勃起功能障碍(ED)。细胞疗法在cni相关ED的治疗中具有巨大的潜力;然而,它需要被优化。在本研究中,我们探讨了脂多糖预处理异体脂肪来源干细胞(L-ADSCs)对cni诱导的大鼠ED的治疗作用。结果:体外实验结果显示,低剂量脂多糖可提高ADSCs的活力,抑制过氧化氢诱导的caspase 3活化,促进细胞迁移。与ADSC上清相比,L-ADSC上清能更好地减轻转化生长因子- β 1蛋白诱导的海绵体平滑肌细胞纤维化。在体内研究中,将其与ADSCs治疗进行了比较,结果表明,L-ADSCs治疗可以通过增加CNI后2周大鼠的平滑肌含量和减轻阴茎纤维化来更好地改善勃起功能。结果可能与海绵体中肝细胞生长因子含量和盆腔神经节中髓鞘碱性蛋白含量的增加有关。结论:L-ADSC治疗可能是CNI后恢复勃起功能的一种有希望的方法。
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引用次数: 3
A rare case of penile schwannomatosis presenting with painful nocturnal penile tumescence. 一例罕见的阴茎神经鞘瘤病表现为疼痛的夜间阴茎肿胀。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-03-21 DOI: 10.1186/s12610-022-00154-y
Chan Ming Tow, Jonathan Tang, Chan Ming Chun, Joe Lee King Chien

Background: Penile schwannoma is a rare tumor. They commonly present as an asymptomatic, painless and slow growing mass. Other presentations include sexual dysfunction, most commonly dyspareunia, followed by erectile dysfunction, abnormal penile curvature or pain with ejaculation.

Case presentation: A 26-year-old male presented atypically with painful nocturnal penile tumescence, along with multiple nodules over the dorsal penis. Excision of multiple penile tumors under general anaesthesia was performed and histopathologic examination revealed benign schwannoma.

Conclusion: Our hypothesis is that the schwannoma lies along the axis of the dorsal penile nerve, and compression of this nerve occurs during his erection causing pain. However, there are limited presentations of painful erections in penile schwannomas, and we hope that future studies can help confirm this theory.

背景:阴茎神经鞘瘤是一种罕见的肿瘤。它们通常表现为无症状、无痛和缓慢生长的肿块。其他表现包括性功能障碍,最常见的是性交困难,其次是勃起功能障碍,阴茎弯曲异常或射精痛。病例介绍:一名26岁男性,表现为夜间阴茎疼痛性肿大,并伴有阴茎背侧多发结节。在全身麻醉下切除多个阴茎肿瘤,组织病理检查显示为良性神经鞘瘤。结论:我们的假设是神经鞘瘤位于阴茎背神经轴上,在勃起时压迫该神经引起疼痛。然而,阴茎神经鞘瘤中勃起疼痛的表现有限,我们希望未来的研究可以帮助证实这一理论。
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引用次数: 0
For patients with non-obstructive azoospermia, the outcome of testicular sperm extraction correlates with self-esteem, sexual health and the quality of the couple's relationship. 对于非阻塞性无精子症患者,睾丸精子提取的结果与自尊、性健康和夫妻关系的质量相关。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-02-16 DOI: 10.1186/s12610-022-00153-z
Marion Bendayan, Emine Sais, Laura Alter, Khadija Fathallah, Monique Jaoul, Pierre Olivier Bosset, Geoffroy Robin, Florence Boitrelle

Background: A very small number of studies have indicated that azoospermia or negative testicular sperm extraction (TESE) outcomes are linked to depression or erectile dysfunction. However, the data are often weak, conflicting and gathered with non-validated questionnaires. Hence, we performed a cross-sectional study of 44 men with non-obstructive azoospermia. Levels of self-esteem and the quality of the couple's sex life and overall relationship were assessed with validated questionnaires before and after the TESE procedure as a function of the TESE outcome.

Results: A positive TESE outcome (n = 24) was associated with a statistically significant increase in self-esteem (particularly with regard to family aspects), sexual health and couples' adjustment quality. In contrast, a negative TESE outcome (n = 20) was associated with statistically significant decreases in self-esteem, erectile function, intercourse satisfaction, orgasmic function, couples' adjustment quality and all aspects of the couple's relationship (consensus, cohesion, satisfaction and affection).

Conclusion: For men with non-obstructive azoospermia (NOA), negative TESE outcomes may have a negative impact on self-esteem and the quality of the couple's sex life and overall relationship. This should be borne in mind when counselling men with NOA and their partners to (ideally) help them to cope with and decrease the harmful impacts of azoospermia and negative TESE.

背景:少数研究表明,无精子症或睾丸精子提取(TESE)阴性结果与抑郁或勃起功能障碍有关。然而,这些数据往往是薄弱的,相互矛盾的,并且是通过未经验证的问卷收集的。因此,我们对44名患有非阻塞性无精子症的男性进行了横断面研究。自尊水平、夫妻性生活质量和整体关系在TESE程序前后通过有效的问卷评估,作为TESE结果的函数。结果:积极的TESE结果(n = 24)与自尊(特别是家庭方面)、性健康和夫妻适应质量的统计学显著增加相关。相反,负的TESE结果(n = 20)与自尊、勃起功能、性交满意度、性高潮功能、夫妻适应质量以及夫妻关系的所有方面(共识、凝聚力、满意度和情感)的统计学显著下降有关。结论:对于非阻塞性无精子症(NOA)的男性,TESE结果的负面影响可能会对自尊、夫妻性生活质量和整体关系产生负面影响。在为患有NOA的男性及其伴侣提供咨询(理想情况下)帮助他们应对和减少无精子症和阴性TESE的有害影响时,应牢记这一点。
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引用次数: 4
Temperature is not a major factor in the differentiation of gonocytes into ad spermatogonia and fertility outcome in congenitally cryptorchid boys. 温度不是影响先天性隐睾男孩性腺细胞向精原细胞分化和生育结果的主要因素。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-01-10 DOI: 10.1186/s12610-021-00152-6
Faruk Hadziselimovic

Spermatogenesis in mammals is a heat-sensitive developmental pathway incompatible with the typical mammalian body temperature of 37 °C. It is thought that this is the reason why the testicles of most mammalian males are outside of the body cavity, in the scrotum, where they function at approximately 33 °C. It has been suggested that the abnormally high temperature environment of cryptorchid testes may lead to impaired testicular development and adult infertility. Here, I summarize the clinical, genetic, and histological evidence that argues against temperature stress and in favor of hypogonadotropic hypogonadism as the underlying cause of adult infertility in cryptorchidism.Patient summary: Infertility and an increased risk of testicular cancer in patients diagnosed with undescended testes are the consequence of a hormonal deficiency rather than temperature-induced cellular damage. Cryptorchidism therefore requires both surgical and hormonal treatment.

哺乳动物的精子发生是一种热敏感的发育途径,与典型的哺乳动物体温37°C不相容。据认为,这就是为什么大多数雄性哺乳动物的睾丸在体腔外,在阴囊内,在那里它们的功能大约在33°C。有研究认为,隐睾异常的高温环境可能导致睾丸发育受损和成人不育。在这里,我总结了临床、遗传和组织学证据,这些证据反对温度应激,支持促性腺功能低下是隐睾症成人不孕的潜在原因。患者总结:诊断为隐睾患者的不育和睾丸癌风险增加是激素缺乏的结果,而不是温度引起的细胞损伤。因此隐睾需要手术和激素治疗。
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引用次数: 3
Effects of unilateral/bilateral amputation of the ischiocavernosus muscle in male rats on erectile function and conception. 单侧/双侧坐骨海绵体肌切除对雄性大鼠勃起功能和受孕的影响。
IF 2.4 3区 医学 Q2 Medicine Pub Date : 2022-01-05 DOI: 10.1186/s12610-021-00151-7
Chengren Gou, Tong Liu, Zongping Chen, Zidong Zhou, Tao Song, Kaiyi Mao, Congcong Chen, Bo Chen

Background: The ischiocavernosus muscle (ICM) encompasses a pair of short pinnate muscles attached to the pelvic ring. The ICM begins at the ischial tuberosity and ends at the crus of the penis while covering the surface of the crus. According to the traditional view, the contraction of the ICM plays an auxiliary role in penile erection. However, we have previously shown that the ICM plays an important role in penile erection through an indirect method of diagnosing erectile dysfunction (ED) caused by ICM injury by observing the infertility of paired female rats. Since intracavernosal pressure (ICP) is the current gold standard for diagnosing ED, this study aimed to amputate unilaterally/bilaterally the ICM to establish an ED model by detecting the ICP, recording the infertility of matching female rats, and comparing the two methods.

Results: Forty sexually mature adult male rats were selected and randomly divided into the following groups: the control group (n = 10), sham operation group (n = 10), unilateral ischiocavernosus muscle (Uni-ICM) amputation group (n = 10), and bilateral ischiocavernosus muscle (Bi-ICM) amputation group (n = 10). Eighty female reproductive rats were randomly assigned to the above groups at a ratio of 2:1. We evaluated the time to conception for the paired female rats and the effects of unilateral/bilateral severing of the ICM on erectile function. The results showed that the baseline and maximum intracavernosal pressure (ICP) in the control group, sham operation group, Uni-ICM amputation group, and Bi-ICM amputation group were 17.44±2.50 mmHg and 93.51±10.78 mmHg, 17.81±2.81 mmHg and 95.07±10.40 mmHg, 16.73±2.11 mmHg and 83.49±12.38 mmHg, and 14.78±2.78 mmHg and 33.57±6.72 mmHg, respectively, immediately postsurgery. The max ICP in the Bi-ICM amputation group was lower than that in the remaining three groups (all P<0.05). The pregnancy rates were 100, 100, 90, and 0% in the control group, sham operation group, Uni-ICM amputation group, and the Bi-ICM amputation group, respectively. The pregnancy rate in the Bi-ICM amputation group was significantly lower than that in the remaining groups (all P<0.05). The time to conception was approximately 7-10 days later in the Uni-ICM amputation group than in the control and sham groups (all P<0.05).

Conclusions: Male rats undergoing Bi-ICM amputation may develop permanent ED, which affects their fertility. In contrast, rats undergoing Uni-ICM amputation may experience transient ED.

背景:坐骨海绵体肌(ICM)包括一对短的羽状肌肉连接到骨盆环。ICM起于坐骨粗隆,止于阴茎小腿,覆盖小腿表面。传统观点认为,阴茎ICM的收缩对阴茎勃起起辅助作用。然而,我们之前通过观察配对雌性大鼠的不育,间接诊断ICM损伤引起的勃起功能障碍(ED),表明ICM在阴茎勃起中起重要作用。由于海绵体内压(intracavernosal pressure, ICP)是目前诊断ED的金标准,本研究拟通过检测ICP,记录配对雌性大鼠的不孕情况,比较两种方法,切除单侧/双侧ICM,建立ED模型。结果:选择40只性成熟成年雄性大鼠,随机分为对照组(n = 10)、假手术组(n = 10)、单侧坐骨海绵体肌(Uni-ICM)截肢组(n = 10)和双侧坐骨海绵体肌(Bi-ICM)截肢组(n = 10)。80只雌性生殖大鼠按2:1的比例随机分为上述两组。我们评估了配对雌性大鼠的受孕时间以及单侧/双侧ICM切断对勃起功能的影响。结果显示,对照组、假手术组、Uni-ICM截肢组和Bi-ICM截肢组术后即刻颅内压(ICP)基线值和最大值分别为17.44±2.50 mmHg和93.51±10.78 mmHg, 17.81±2.81 mmHg和95.07±10.40 mmHg, 16.73±2.11 mmHg和83.49±12.38 mmHg, 14.78±2.78 mmHg和33.57±6.72 mmHg。Bi-ICM截肢组的最大ICP低于其他三组(均为p)结论:Bi-ICM截肢的雄性大鼠可能出现永久性ED,影响其生育能力。相比之下,接受Uni-ICM截肢的大鼠可能会出现短暂性ED。
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引用次数: 0
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Basic and Clinical Andrology
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